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Mitochondrial ATP-sensitive K+ channels are closely linked to cardioprotection and are potential therapeutic targets during ischemia reperfusion (IR) injury. The renal outer medullary K+ channel isoform 2 (ROMK2) is an ATP-sensitive K+ channel found in the mitochondria of cardiomyocytes. While the germline knockout of ROMK does not mediate myocardial IR injury, the effect of ROMK loss of function on IR injury in the adult myocardium is unknown. By using a selective small molecule inhibitor of ROMK, we paradoxically found that mouse hearts were protected from IR injury after ROMK inhibition compared to vehicle-treated animals. In addition, we found that ROMK inhibition leads to exaggerated mitochondrial uncoupling and increased ROS production. Phosphatidylinositol 4,5-bisphosphate (PIP2), an activator of ROMK, increased the effect of ATP to hyperpolarize cardiac mitochondrial membrane potential. ROMK inhibition also increased mitochondrial swelling in the absence of ATP. In conclusion, pharmacologic ROMK inhibition protects the murine heart from IR injury and may promote a phenotype of enhanced mitochondrial matrix K+. ROMK may be more important during conditions that promote mitochondrial matrix K+ efflux than influx. Further research to understand its role in mitochondrial K+ handling and as a therapeutic target in IR injury is needed.

ObjectivesThere is minimal literature examining the association of sepsis with out-of-hospital cardiac arrest (OHCA). Using a large national database, we aimed to quantify the risk of OHCA among sepsis patients after hospital discharge.DesignPopulation-based cohort study.SettingNationwide sepsis cohort retrieved from the National Health Insurance Research Database of Taiwan between 2000 and 2013.ParticipantsWe included 17 304 patients with sepsis. After hospital discharge, 144 patients developed OHCA within 30 days and 640 between days 31 and 365.Primary and secondary outcome measuresThe main outcomes were OHCA events following hospital discharge for sepsis. To evaluate the independent association between sepsis and OHCA after a sepsis hospitalisation, we constructed two non-sepsis comparison cohorts using risk set sampling and propensity score matching techniques (non-infection cohort, non-sepsis infection cohort). We plotted the daily number and daily risk of OHCA within 1 year of hospital discharge between sepsis and matched non-sepsis cohorts. We used Cox regression to evaluate the risk of early and late OHCA, comparing sepsis to non-sepsis patients.ResultsCompared with non-infected patients, sepsis patients had a higher rate of early (HR 1.66, 95% CI: 1.27 to 2.16) and late (HR 1.19, 95% CI: 1.06 to 1.33) OHCA events. This association was independent of age, sex or cardiovascular history. Compared with non-sepsis patients with infections, sepsis patients had a higher rate of both early (HR 1.28, 95% CI: 1.00 to 1.63) and late (HR 1.13, 95% CI: 1.01 to 1.27) OHCA events, especially among patients with cardiovascular disease (OR 1.35, 95% CI: 1.01 to 1.81).ConclusionsSepsis patients had increased risk of OHCA compared with matched non-sepsis controls, which lasted up to 1 year after hospital discharge.

Among 45 CpcPH/heart failure with preserved ejection fraction participants, 11 with normal left atrium (compared to 34 with abnormal left atrium, p  < 0.05 for all) had low left ventricle (LV) transmural pressure (2.9 ± 2.4 vs. 6.2 ± 2.9 mmHg), and increased right ventricle (RV):LV ratio (2.41 ± 1.09 vs. 1.46 ± 0.66) and interventricular septal angle (149 ± 8 vs. 136 ± 10), indicating exaggerated ventricular interdependence from a dilated RV.

The goal of hormonal therapy in treating gender dysphoria is to maintain cross-sex hormone levels in the normal physiological range for the desired gender. Estrogen is the mainstay of hormonal therapy for male to female transgender patients. Efavirenz, a non-nucleoside reverse-transcriptase inhibitor, has been one of the most commonly prescribed antiretroviral therapies (ARTs). However, this regimen has also given rise to the most clinically significant drug–drug interactions between ARTs and hormone-based contraceptives. We discuss here three transgender HIV-positive women in whom efavirenz effected the metabolism of orally administered estradiol (and probably medroxyprogesterone).

Idiopathic pneumonia syndrome (IPS) is a rare but deadly complication of hematopoietic stem cell transplantation (HSCT). This study characterized the incidence and risk factors for IPS after HSCT in Taiwan. Data from January 2009 to February 2019 was collected from the Taiwan Society of BMT national registry. Forty-three (1.1%) of 3924 HSCT patients who developed IPS were identified. Incidence of IPS was lower in patients who received autologous HSCT than patients who received allogeneic HSCT (0.68% vs 1.44%, P = 0.022). Multivariate analysis showed that use of TBI and intravenous busulfan in the conditioning regimen were each independent predictor of IPS after HSCT. In addition, development of IPS was significantly associated with increased risk of death in the first 120 days post-HSCT (HR, 2.09; 95% CI, 1.08 to 4.05, P = 0.029) and 2 years post-HSCT (HR, 1.65; 95% CI, 1.07 to 2.542, P = 0.023), but not beyond 2 years post-HSCT. However, survival outcomes did not differ significantly between patients with IPS who received autologous versus allogeneic HSCT (P = 0.52). In conclusion, despite the relatively low incidence of post-HSCT IPS in Taiwan, mortality remains high. The results of this study will help to identify high-risk patients for early intervention and guide future therapeutic research.

Background: Little is known about the risk of in-hospital cardiac arrest (IHCA) among patients with sepsis. We aimed to characterize the incidence and outcome of IHCA among patients with sepsis in a national database. We then determined the major risk factors associated with IHCA among sepsis patients. Methods: We used data from a population-based cohort study based on the National Health Insurance Research Database of Taiwan (NHRID) between 2000 and 2013. We used Martin's implementation that combined the explicit ICD-9 CM codes for sepsis and six major organ dysfunction categories. IHCA among sepsis patients was identified by the presence of cardiopulmonary resuscitation procedures. The survival impact was analyzed with the Cox proportional-hazards model using inverse probability of treatment weighting (IPTW). The risk factors were identified by logistic regression models with 10-fold cross-validation, adjusting for competing risks. Results: We identified a total of 20,022 patients with sepsis, among whom 2,168 developed in-hospital cardiac arrest. Sepsis patients with a higher burden of comorbidities and organ dysfunction were more likely to develop in-hospital cardiac arrest. Acute respiratory failure, hematological dysfunction, renal dysfunction, and hepatic dysfunction were associated with increased risk of IHCA. Regarding the source of infection, patients with respiratory tract infections were at the highest risk, whereas patients with urinary tract infections and primary bacteremia were less likely to develop IHCA. The risk of IHCA correlated well with age and revised cardiac risk index (RCRI). The final competing risk model concluded that acute respiratory failure, male gender, and diabetes are the three strongest predictors for IHCA. The effect of IHCA on survival can last 1 year after hospital discharge, with an IPTW-weighted hazard ratio of 5.19 (95% CI: 5.06, 5.35) compared to patients who did not develop IHCA. Conclusion: IHCA in sepsis patients had a negative effect on both short- and long-term survival. The risk of IHCA among hospitalized sepsis patients was strongly correlated with age and cardiac risk index. The three identified risk factors can help clinicians to identify patients at higher risk for IHCA.